Architectural confinement and seasonal forcing shape cross-domain pathogen-associated assemblages in complex built environments.

Airborne microbial pathogens in built environments (BEs) may pose health threats, yet the ecological mechanisms governing their assembly and persistence across interconnected architectural spaces are less studied. Here, we conducted a year-long, multi-spatial investigation across a university building complex, sampling the exhaust outlets of three indoor environments and adjacent outdoor inlets. By integrating the 16S rRNA gene and ITS sequencing from 437 paired bacterial-fungal samples, we characterized the spatiotemporal dynamics of airborne opportunistic pathogen-containing genera. Our study showed that spatial filtering emerged as the dominant determinant of pathogen community structure, with confined elevator environments serving as reservoirs of potential pathogens, with limited but continuous microbial influx from surrounding spaces. Some potential pathogens exhibited distinct seasonal dynamics, as exemplified by pathogen-associated fungal genera such as Fusarium, which peaked in autumn and winter, possibly driven by enhanced aerosol persistence and dispersal under cooler, drier conditions. In contrast, the bacterial counterparts exhibited greater temporal resilience, with key taxa such as Listeria actively transcribed during winter, predisposing them to increased relative abundance in spring. Cross-domain ecological networks further revealed dynamic associations among potential pathogens, centered on the skeletal structure mediated by the keystone fungal genus Aspergillus, suggesting that coordinated microbial associations may reinforce their persistence across seasons. Together, our findings suggest that the dynamics of pathogen-containing genera within BEs arise from the coupled effects of spatial filtering, climatic modulation, and microbial associations. These results provide a foundation for transitioning from static environmental control toward predictive pathogen management in BEs.IMPORTANCEBuilt environments (BEs) are the primary settings of human microbial exposure, yet the ecological principles governing the persistence of airborne pathogens across interconnected indoor spaces remain poorly resolved. By integrating bacterial and fungal community dynamics across spatial environments over four seasons, this year-long study demonstrates that the ecology of airborne pathogen-associated taxa is not static but is instead mediated by a complex interplay of spatial, climatic, and biological forces. Our findings identify enclosed, high-transit elevator spaces as critical hotspots for the accumulation of potential pathogens and highlight the role of seasonal ecological reorganization in driving airborne health risks. More broadly, this work establishes a system-level ecological framework for understanding the dynamics of airborne pathogen-associated taxa in BEs and provides a conceptual basis for developing more adaptive strategies for indoor microbial risk management.